Juvenile hyperthyroidism: an experience.

OBJECTIVE: To analyze the clinical profile of juvenile hyperthyroidism at presentation, their treatment outcome; predictors of remission and relapse. METHODS: Retrospective analysis of medical records of 56 patients with juvenile hyperthyroidism seen over a period of 16 years. A cohort of 38 females and 18 males with mean (+/-SD) age of 14.9 +/- 3.4 years (range 3 to 18 years) was analyzed. RESULTS: Majority of patients was in the age group of 12-16 years. Common symptoms observed at presentation were weight loss (82.1%), excessive sweating (78.6%), heat intolerance (76.8%), increased appetite (73.2%) and diarrhea in 48.2%. In addition, accelerated linear growth was observed in 7.1% of patients. Goiter was present in 98.2% of children; 94.5% of which was diffuse and 4.8% was multinodular. The mean ((+/-SD) T3 was 4.8 +/- 3.4 ng/mL (N, 0.6-1.6), T4 was 218 +/- 98 ng/mL (N, 60-155) and TSH was 0.44 +/- 0.36 (N, 0.5-5.5 microIU/mL). TMA positivity seen in 36.9% of patients. All patients were treated with carbimazole; subsequently 4 patients required thyroidectomy and one required radioactive iodine ablation. Mean (+/-SD) duration of follow-up in our patients was 4.9 +/- 3 years, ranging between 1.6 to 16 years and mean (+/-SD) duration of treatment was 34.4 +/- 22.6 months (range 12 to 120 months). Mean (+/-SD) duration to achieve euthyroidism was 5.2 +/- 4.7 months, ranging between 1-33 months. On intention to treat analysis, remission with carbimazole was achieved in 47.6%, remaining patients failed to achieve remission with drug treatment. CONCLUSION: Graves disease is the commonest cause of juvenile hyperthyroidism. Carbimazole is safe, effective, cheap, and easily available form of therapy. It is occasionally associated with serious side effects but requires prolonged follow up.

Efficacy of once- or twice-daily extended release metformin compared with thrice-daily immediate release metformin in type 2 diabetes mellitus.

BACKGROUND: The extended-release formulation of metformin (MXR) prolongs drug absorption in the upper gastrointestinal tract and permits once-daily dosing in patients with type 2 diabetes mellitus (T2DM). This newer formulation may enhance patient compliance with oral therapy compared to conventional immediate-release metformin (MIR) in T2DM. OBJECTIVES: To analyse whether a switch from thrice daily MIR to once or twice daily MXR wouldachieve comparable degrees of glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted an open study of the efficacy and tolerability of MXR in 40 patients with T2DM who had achieved moderate or good glycemic control with MIR alone or in combination with other antihyperglycemic agents. After a lead in period of 3 months patients were switched over to a specific brand of MIR at baseline (Visit 0). Patients were subsequently followed for 4 more visits. These visits were done monthly, after taking MIR in a dose of 1-2 g/day (Visit 1); MXR as a single dose at dinner but 0.5 g less than baseline dose of MIR (Visit 2); MXR, 1-2 g/day as a single dose at bedtime, with strength same as that of baseline dose of MIR (Visit 3); and MXR, 1-2 g/day in two divided doses keeping dose same as baseline MIR (Visit 4). Glycemic control was assessed by a four-point glucose profile (fasting and three postprandial levels) at each visit. RESULTS: At visit 2, when patients had been on 500 mg lesser dose of MXR for 1 month, glucose profile worsened. However, glycemic control, at visit 3, returned to earlier levels when dose of MXR was increased back to original dose. Overall the MXR formulation was well tolerated with minor gastrointestinal adverse effects, reported by only 3 patients. CONCLUSION: Patients with T2DM who had been receiving thrice-daily MIR achieved comparable glycemic control when therapy was switched to once- or twice-daily MXR at the same total daily dose.

Clinical and etiological profile of hyperprolactinemia--data from a tertiary care centre.

OBJECTIVE: To study the clinical presentation and etiology of hyperprolactinemia, a common disorder encountered in endocrine practice. METHODS: We analyzed the clinical data, hormone profile and imaging reports of 187 females with documented hyperprolactinemia, over a period of 6 years (5 years retrospective analysis and one year prospective study). RESULTS: Majority of the 187 subjects studied presented in 3rd or 4th decade. Galactorrhoea was the commonest presenting symptom occurring in 159 subjects (85%), followed by amenorrhea in 68.9%; both amenorrhea and galactorrhea were seen in 45.4%. A microprolactinoma was demonstrated in 67 patients (35.8%), a nonfunctioning pituitary macroadenoma with stalk hyperprolactinemia occurred in 30 patients (16%) and polycystic ovarian disease was documented in 24 (12.8%). In 52 patients (27.8%) no apparent cause could be ascertained. CONCLUSIONS: Syndrome of amenorrhea and/or galactorrhea is the commonest presentation in hyperprolactinemia. Microprolactinoma was the most frequent identifiable etiology followed by idiopathic and stalk hyperprolactinemia in our series.

Prevalence and pattern of sick euthyroid syndrome in acute and chronic non-thyroidal illness--its relationship with severity and outcome of the disorder.

BACKGROUND: Non-thyroidal illness is a common cause of alterations in thyroid hormone economy in absence of underlying intrinsic thyroid disorder. OBJECTIVE: To study the prevalence and pattern of alterations in thyroid hormone economy in various non-thyroidal illnesses in our region and also to correlate these alterations with the severity and outcome of the non-thyroidal illness. MATERIAL AND METHODS: We analyzed circulating T3, T4, TSH in 382 patients with non-thyroidal illness (285 acute and 97 acute on chronic) and correlated the alterations with severity and outcome of the non-thyroidal disorder. The patients had one or more organ failure at the time of enrollment to the study. The hormones were estimated at the onset of sickness, and at 3rd and 24th week. T3, T4 and TSH in 75 age and sex matched euthyroid subjects were taken as controls. RESULTS: T3 (mean +/- SEM) was significantly reduced at the onset of illness, in both acute and chronic patient groups (1.61 +/- 0.05 nmol/l) compared to that in the controls (3.17 +/- 0.06 nmol/l). In spite of clinical improvement in most instances, T3 continued to remain low in the 3rd week (1.49 +/- 0.11 nmol/ l) but increased (2.14 +/- 0.09 nmol/l) in 24th week. Low T3 was found in 93 (32.6%) cases with acute illness in 20 (20.6%) cases with chronic illness. A combination of low T3 and T4 was found in 35 (12.3%) of cases with acute and 15 (15.5%) with chronic illness. Although serum TSH showed noticeable fall and rise in some individuals, no significant difference in mean TSH was observed during any period of illness compared to that in the controls. Severity of illness correlated with decrease in T3 (r=0.58) and T4 (r=0.38). A low T3 and T4 with low or undetectable TSH were associated with increased mortality. At the onset of acute illness low T3 was seen in 113 (29.6%, low T3 -low T4 in 50 (13.1%), high T4 in 28 (7.3%) lowT3-lowT4- low TSH in 10 (2.6%) and low T4 alone in 4 (1%) patients. Fifty one 1 (13.4%) of our patients demonstrated alterations in TSH in presence of normal T3 and T4-26 patients had decreased TSH while as 25 had increased TSH. Of 118 patients who followed at 24 weeks, 11 (9.3%) had low T3, 7(5.9%) had low T3- low T4 and 13 (11%) had elevated TSH. CONCLUSION: Pattern and prevalence of sick euthyroid syndrome in this part of the world, a recognized iodine deficient region, appears to be similar to that reported elsewhere. Important finding in our study was higher percentage of TSH elevation, which we believe to reflect the underlying iodine deficiency state of our community. Besides a significant number of subjects persisted with alterations in thyroid functions even after 6 months of therapy. Though the severity of thyroid hormone derangement correlated with severity of sickness, the derangement was similar in acute vs. acute on chronic nonthyroidal illnesses.

Diffuse abdominal lipomatosis.

We report a 22-year male who developed progressive distension of abdomen, clinically diagnosed as ascites. A diagnosis of abdominal lipomatosis was made on the basis of CT evidence of excessive fatty tissue in abdominal cavity which was confirmed on laparotomy.

Response of regimens of insulin therapy in type 2 diabetes mellitus subjects with secondary failure.

OBJECTIVE: To find the response of various regimen of combination therapy (Insulin and Glibenclamide) in type 2 diabetes mellitus subjects who failed to respond to maximum doses of glibenclamide (GBC) plus phenformin. METHODS: A total of 188 subjects with secondary sulfonylurea failure who failed to respond to maximum doses of GBC and phenformin were randomised to receive one of the four regimens. Group A (50 patients) received two doses of insulin; Group B (49 patients) received two doses of insulin and GBC 20 mg/day; Group C (43 patients) received morning dose of insulin with GBC 20 mg/day; and Group D (46 patients) received evening dose of insulin with GBC 20 mg/day. Insulin dose was adjusted to achieve an acceptable blood glucose control. Control of diabetes was revaluated at three months post-treatment period. RESULTS: Age, duration of diabetes, weight, body mass index (BMI) and biochemical parameters were comparable in all four groups at admission. Dose of insulin was 0.83 +/- 0.07, 0.86 +/- 0.06, 0.46 +/- 0.04 and 0.39 +/- 0.03 units/Kg/day in groups A, B, C and D, respectively. Comparing groups A and B, we found that the dose of insulin (IU/kg/day) required to achieve acceptable fasting blood glucose (FBG) did not differ significantly. Similarly, comparison between Groups C and D did not reveal any significant difference in insulin dose. Mean hospital stay required to achieve an acceptable FBG was 8.42 +/- 0.34, 11.95 +/- 1.11, 8.59 +/- 0.61 and 7.10 +/- 0.48 days in groups A, B, C and D, respectively (p = 0.013). On comparing the four treatment regimens, at three months follow-up, there was a significant increase in bodyweight in Group C; also there was an increase in fasting blood glucose in all the groups except in Group D. CONCLUSIONS: Continuation of GBC in type 2 diabetes mellitus subjects who fail to respond to maximum doses of GBC plus phenformin and who need two doses of insulin for control has no added advantage over giving insulin alone. In subjects controlled on a single dose of insulin with glibenclamide it is preferable to give an evening dose rather than a morning dose.

A critical evaluation of signs and symptoms in the diagnosis of Addison's diseases.

OBJECTIVES: To determine the usefulness of clinical symptoms and signs in the diagnosis of Addison's disease. METHODOLOGY: A retrospective, hospital based study from analysis of case records of over 12 years period (1988-1999). Individual or groups of signs and symptoms in 66 patients of confirmed Addison's diseases were compared with 76 subjects with normal ACTH stimulation test, when clinical presentations were similar. RESULTS: Age spectrum of the two groups was similar. Signs and symptoms like weakness, weight loss, gastro-intestinal disturbances, skin/mucosal pigmentation and blood pressure were not statistically different between the two groups. Similarly blood glucose, sodium and potassium were not different between the two groups. Combination of three or more symptoms/signs had a high predictive value of diagnosing the disease than any individual or a combination of < 3 signs/symptoms (P=0.033). CONCLUSIONS: Combination of skin and mucosal pigmentation with gut disturbances and weight loss carried high predictive value in diagnosis of Addison's disease, while individual sign and symptom has poor differentiating value.

Clinical and aetiological profile of early onset diabetes mellitus: data from a tertiary care centre in the Indian subcontinent.

BACKGROUND: Type 2 diabetes mellitus (DM) in youth is emerging as a serious clinical entity and its incidence has increased over the years. AIM: To analyse the causes of DM in the age group of <40 years of age. SETTINGS AND DESIGN: Tertiary care centre; retrospective analysis of data from January 1990 to December 1999. SUBJECTS AND MATERIAL: Analysis of data of all the subjects of DM in whom disease started before the 40th birthday. RESULTS: 724 subjects were detected to have diabetes mellitus before their 40th birthday. Of these, 205 had Type 1, 174 had Type 2 and 48 had fibrocalculous pancreatic diabetes. Males outnumbered in Type 1 and fibrocalculous pancreatic diabetes while as females in Type 2 diabetes mellitus. Chronic complications were more common in Type 2 diabetes mellitus. CONCLUSION: Type 2 diabetes mellitus is becoming an important cause of diabetes in subjects with onset of disease at younger age.

Prevalence of obesity in adults--an epidemiological study from Kashmir Valley of Indian Subcontinent.

OBJECTIVE: Obesity is a health problem in the majority of the developed countries and is emerging as a serious problem in the developing countries. In this study we examined 5083 Kashmiri adults to determine the prevalence of obesity. METHODS: In this epidemiological study, after multistage sampling procedure from all the six districts of Kashmir Valley, 5083 Kashmiri adults (males and non-pregnant females of > or = 40 years age) were examined for body mass index (BMI) and waist to hip ratio (WHR). RESULTS: Out of 5083 study subjects, 2496 were males and 2587 were females. BMI ranged between 14.6 to 38.5 kg/m2 in males and between 13.6 to 42.6 kg/m2 in females. BMI in females was comparatively more than that in males (23.88 +/- 3.94 Vs 22.30 +/- 3.11, p < 0.001). WHR ranged between 0.68 to 1.16 in males and between 0.65 to 1.16 in females. Again females had comparatively more WHR than their male counterparts (0.935 +/- 0.055 vs 0.926 +/- 0.055, P < 0.001). According to BMI, the overall prevalence of obesity in the study population was 15.01%; the prevalence of obesity in males was 7.01% and in females 23.69%. CONCLUSIONS: We conclude that obesity is a growing problem even in developing regions like ours. It is more common in females and in urban population.

Pregnancy in premature ovarian failure: a possible role of estrogen plus progesterone treatment.

Premature ovarian failure (POF) is a common occurrence in women during their reproductive years. There is paucity of data on spontaneous ovulation and subsequent pregnancies in such women. In this report, we describe three women with POF, two of whom had spontaneous conceptions and the third resumed spontaneous regular menstrual cycles. All these women had received oestrogen-progesterone tablets for many cycles (ethyl oestradiol 0.05 mg and levonorgestrel 0.25 mg a day, 21 days a month). We speculate about the possibility of elevated gonadotrophins causing down regulation of gonadotrophin receptors and restoration of the sensitivity of the few remaining ovarian follicles by lowering of serum gonadotrophins with oestrogen therapy.

Seroprevalence of toxoplasmosis in women with recurrent abortions/neonatal deaths and its treatment outcome.

Toxoplasmosis, a parasitic infection, varies in its prevalence in various countries. Some studies have suggested its role in the causation of abortions. We reviewed the records of Microbiology Department at Sher-i-Kashmir Institute of Medical Sciences, Srinagar (Kashmir) and found that out of 2371 women with recurrent abortions and 310 women with neonatal deaths tested for IgM antibody against toxoplasma, 1260 (53.14%) and 215 (69.35%) tested positive respectively. One hundred and twenty-two women with recurrent abortions and 55 women with neonatal deaths who had tested positive for IgM antibody were followed during subsequent pregnancy and were treated with spiramycin; 115 94.26%) in current abortion group and 35 (63.64%) in neonatal death group delivered normal babies. We discuss the role of seropositivity for toxoplasma in women during reproductive period.

Pregnancy in Sheehan's syndrome: a report of three cases.

Postpartum pituitary necrosis (Sheehan's syndrome) is a relatively common clinical disorder in developing and underdeveloped areas of the world. Sheehan's syndrome has a spectrum of presentations. Spontaneous pregnancy in such patients is a rare occurrence. Three patients with clinical and hormonal evidence of postpartum pituitary necrosis conceived spontaneously during the follow up period. Pregnancy though rare may occur either due to sparing or recovery of gonadotroph function in such patients.

Regular ovulatory menstrual cycles in a case of Sheehan's syndrome.

In this report we describe an unusual case of postpartum pituitary necrosis who had clinical and biochemical suggestion of decreased thyrotroph, somatotroph, lactotroph, and corticotroph reserve but continued to have regular ovulatory menstrual cycles.